Optimal Control of SonoVue Microbubbles to Estimate Hydrostatic Pressure.

Amanda Q X Nio,Daniel Fuster,Kirsten Christensen-Jeffries,Jason L Raymond,Alessandro Faraci,Pablo Lamata,Mark J Monaghan,Flemming Forsberg,Robert J Eckersley

doi:10.1109/tuffc.2019.2948759

Abstract

The measurement of cardiac and aortic pressures enables diagnostic insight into cardiac contractility and stiffness. However, these pressures are currently assessed invasively using pressure catheters. It may be possible to estimate these pressures less invasively by applying microbubble ultrasound contrast agents as pressure sensors. The aim of this study was to investigate the subharmonic response of the microbubble ultrasound contrast agent SonoVue (Bracco Spa, Milan, Italy) at physiological pressures using a static pressure phantom. A commercially available cell culture cassette with Luer connections was used as a static pressure chamber. SonoVue was added to the phantom, and radio frequency data were recorded on the ULtrasound Advanced Open Platform (ULA-OP). The mean subharmonic amplitude over a 40% bandwidth was extracted at 0–200-mmHg hydrostatic pressures, across 1.7–7.0-MHz transmit frequencies and 3.5%–100% maximum scanner acoustic output. The Rayleigh–Plesset equation for single-bubble oscillations and additional hysteresis experiments were used to provide insight into the mechanisms underlying the subharmonic pressure response of SonoVue. The subharmonic amplitude of SonoVue increased with hydrostatic pressure up to 50 mmHg across all transmit frequencies and decreased thereafter. A decreasing microbubble surface tension may drive the initial increase in the subharmonic amplitude of SonoVue with hydrostatic pressure, while shell buckling and microbubble destruction may contribute to the subsequent decrease above 125-mmHg pressure. In conclusion, a practical operating regime that may be applied to estimate cardiac and aortic blood pressures from the subharmonic signal of SonoVue has been identified.

Highlights

M ICROBUBBLE based ultrasound contrast agents are currently used in the clinic to complement standard B-mode imaging across multiple organs and systems in the human body, including the heart, breast and liver [1]–[4]
The subharmonic signal of ultrasound contrast agents can be delineated into three distinct phases: (i) occurrence, (ii) growth and (iii) saturation [13], [14]
We investigated the subharmonic response of the microbubble ultrasound contrast agent SonoVue at 0–200 mmHg hydrostatic pressures using a static pressure phantom

Summary

Introduction

M ICROBUBBLE based ultrasound contrast agents are currently used in the clinic to complement standard B-mode imaging across multiple organs and systems in the human body, including the heart, breast and liver [1]–[4]. The ultrasound contrast agents Levovist, Optison, Definity, ZFX and Sonazoid have been found to generate a subharmonic signal that is linearly and negatively correlated to static hydrostatic pressures from 0–186 mmHg [10]. This phenomenon may be due to changes in bubble surface tension and shell buckling [11], [12], and is affected by ultrasound settings such as transmit frequency, pulse length and acoustic pressure. An acoustic pressure within the growth phase has been shown to be necessary to elicit a strong negative linear relationship between the subharmonic amplitude of ultrasound contrast agents and hydrostatic pressure [6], [13]

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